Maternal Obesity and Gestational Diabetes: Impact on Metabolome

孕产妇肥胖和妊娠糖尿病：对代谢组的影响

• 批准号: 8638966
• 负责人: William L Lowe
• 金额: $ 43.18万
• 依托单位: NORTHWESTERN UNIVERSITY AT CHICAGO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-04-01 至 2017-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638966
• 关键词: Address; Adult; American; Amino Acids; Biological; Birth; Birth Weight; Body fat; Body mass index; C-Peptide; Caribbean region; Child; Childhood; Consensus; Data; Data Collection; Diabetes Mellitus; Diagnosis; Emerging Technologies; Enrollment; Environment; Environmental Exposure; European; Exhibits; Fasting; Fetal Development; Fetal Growth; Fetus; Frequencies; Funding; Future; Genetic; Gestational Diabetes; Glucose; Goals; Health; Human Resources; Hyperglycemia; Individual; International; Laboratories; Lipids; Mass Fragmentography; Mass Spectrum Analysis; Measures; Metabolic; Metabolic Diseases; Mexican Americans; Molecular Weight; Mothers; Neonatal; Newborn Infant; OGTT; Obesity; Observational Study; Outcome; Outcome Study; Physiological; Placenta; Pregnancy; Pregnancy Outcome; Protocols documentation; Resources; Risk; Sampling; Secondary to; Serum; Sum; Technology; Testing; Third Pregnancy Trimester; Time; Training; United States National Institutes of Health; Woman; acylcarnitine; base; cohort; fetal; glucose metabolism; glucose tolerance; impaired glucose tolerance; improved; instrument; insulin sensitivity; maternal diabetes; metabolomics; obesity risk; offspring; public health relevance; trait

DESCRIPTION (provided by applicant): Offspring of mothers with obesity and/or pre-existing or gestational diabetes mellitus (GDM) during pregnancy are at increased risk for obesity and altered glucose metabolism as children and adults, leading to a proposed "transgenerational cycle of obesity and diabetes" wherein maternal diabetes and/or obesity in pregnancy beget more diabetes and obesity. The mechanisms underlying these risks are not known, but the mother's metabolic profile impacts the intrauterine milieu of the developing fetus as glucose and other molecules cross the placenta and impact fetal growth and development. We are hypothesizing that analytes comprising distinct metabolic signatures will demonstrate association with newborn anthropometric traits as well as maternal glycemic and anthropometric traits and that offspring of mothers with GDM (defined using the new International Association of Diabetes and Pregnancy Study Groups (IADPSG) criteria) and/or obesity will exhibit a metabolic profile similar to that associated with newborn adiposity, regardless of their adiposity. We will address this hypothesis using metabolomics, a technology capable of defining the metabolic profile present in different physiologic or pathophysiologic conditions, and a unique resource, stored serum samples from ~23,000 mothers and their offspring who were enrolled in the Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study. The General Aim of the proposed HAPO Metabolomics Study is to use a targeted mass spectrometry- based platform to measure amino acids, acylcarnitines, and conventional metabolites and a gas chromatography:mass spectrometry-based non-targeted platform to analyze a wide variety of metabolites to define the metabolic profile of 1,600 Northern European ancestry, Afro-Caribbean, Mexican-American and Thai mother-offspring pairs at ~28 weeks gestation (in mothers) and birth (in offspring). The following Specific Aims will be addressed. (i) To test the hypothesis that distinct metabolic signatures are independently associated with maternal metabolic traits (fasting, 1 hr., and 2 hr. glucose and insulin sensitivity) determined by an oral glucose tolerance test (OGTT) and body mass index (BMI) at the time of the OGTT. (ii) To test the hypothesis that the above metabolic profiles will be evident during pregnancy in mothers of newborns at increased risk for metabolic diseases by determining metabolic profiles for mothers that independently associate with GDM and obesity during pregnancy. (iii) To test the hypothesis that a distinct metabolic signature in mothers and newborns is associated with newborn anthropometric traits at birth including birth weight, sum of skinfolds, and percent body fat. (iv) To test the hypothesis that newborns at risk for metabolic diseases in childhood and/or adulthood secondary to maternal GDM and/or obesity have distinct metabolic profiles at birth by determining metabolic profiles in newborns that independently associate with GDM and maternal obesity during pregnancy. Together, these studies will have an important impact on our understanding of the metabolic underpinnings of the increased risk of metabolic diseases in newborns of mothers with hyperglycemia and/or obesity.

描述（由申请人提供）：在怀孕期间患有肥胖症和/或先前存在的或妊娠期糖尿病（GDM）的母亲的后代在儿童和成人时具有肥胖症和改变的葡萄糖代谢的增加的风险，导致提出的“肥胖症和糖尿病的跨代循环”，其中怀孕期间的母亲糖尿病和/或肥胖症产生更多的糖尿病和肥胖症。这些风险的潜在机制尚不清楚，但母亲的代谢特征会影响发育中胎儿的宫内环境，因为葡萄糖和其他分子穿过胎盘并影响胎儿的生长和发育。我们假设，包含不同代谢特征的分析物将证明与新生儿人体测量特征以及母体血糖和人体测量特征的关联，并且患有GDM（使用新的国际糖尿病和妊娠研究组协会（IADPSG）标准定义）和/或肥胖的母亲的后代将表现出与新生儿肥胖相关的代谢谱相似的代谢谱，而不管其肥胖。我们将使用代谢组学来解决这一假设，代谢组学是一种能够定义不同生理或病理生理条件下存在的代谢谱的技术，以及一种独特的资源，来自约23，000名参加高血压和不良妊娠结局（HAPO）研究的母亲及其后代的血清样本。拟定HAPO代谢组学研究的总体目的是使用基于靶向质谱的平台测量氨基酸、酰基肉毒碱和常规代谢物，并使用基于气相色谱：质谱的非靶向平台分析各种代谢物，以确定1，600例北方欧洲血统、非洲-加勒比、墨西哥-美国和泰国母子对在妊娠（母体）和出生（后代）约28周时的代谢特征。将讨论以下具体目标。(i)为了检验不同的代谢特征与母体代谢特征独立相关的假设（空腹，1小时，和2小时的葡萄糖和胰岛素敏感性）和OGTT时的体重指数（BMI）。(ii)通过测定与妊娠期GDM和肥胖独立相关的母亲的代谢谱，检验上述代谢谱在新生儿代谢疾病风险增加的母亲妊娠期间明显存在的假设。(iii)检验母亲和新生儿不同的代谢特征与新生儿出生时的人体测量特征（包括出生体重、皮褶总和和体脂百分比）相关的假设。(iv)通过测定与妊娠期GDM和母体肥胖独立相关的新生儿代谢谱，检验以下假设：有儿童期和/或成年期继发于母体GDM和/或肥胖的代谢疾病风险的新生儿在出生时具有不同的代谢谱。总之，这些研究将对我们理解高血糖和/或肥胖母亲的新生儿代谢疾病风险增加的代谢基础产生重要影响。